Extracorporeal Membrane Oxygenation (ECMO) Nursing CE Course

recognized that ECMO required continuous anticoagulation to prevent adverse effects, launching the start of EMCO as it is used today (Makdisi & Wang, 2015; Vyas & Bishop, 2022; Wrisinger & Thompson, 2022).

Some of the first reported uses of ECMO were within the neonatal population. In the late 1960s, a few ECMO cases were reported for neonates for cardiopulmonary bypass and cardiac surgery. The first reported use of long-term ECMO (i.e., up to 30 days) in adults did not occur until 1972, when it was used for respiratory support for an adult with post-traumatic severe respiratory failure. The first successful use of ECMO in neonates with severe respiratory distress occurred in 1975. In 1981, Kolobow and colleagues conducted one of the first randomized controlled trials (RCTs) comparing ECMO to the standard of care for patients with acute respiratory distress syndrome (ARDS). However, the successful use of ECMO in this study was contradicted by an RCT conducted in 1994 by Morris and colleagues, which failed to show an advantage of ECMO use compared to conventional management with MV for ARDS. These researchers found survival rates with ECMO to be 33% compared to 42% in patients receiving MV. In the early 2000s, silicone membranes and polypropylene hollow fiber oxygenators were replaced with polymethylpentene (PMP) oxygenators that were easier to use, more durable, and provided superior gas exchange and less trauma to the blood (Makdisi & Wang, 2015; Vyas & Bishop, 2022; Wrisinger & Thompson, 2022).

Despite the inconsistent evidence to support the use of ECMO, some healthcare facilities in the US and Europe continued to use ECMO with standard MV in certain patients successfully. Then in 2009, the conventional ventilatory support versus ECMO for severe adult respiratory failure (CESAR) trial was published. This study was the first large-scale RCT, including 180 patients from 68 centers. The researchers found that patients treated with ECMO showed significantly better outcomes than conventional treatment, including reduced mortality rates and severe disability at 6 months. Since the CESAR trial, the use of ECMO has increased significantly globally. ECMO was used in 83 healthcare centers in 1990, increasing to 492 centers in 2020 (Makdisi & Wang, 2015; Vyas & Bishop, 2022; Wrisinger & Thompson, 2022).

Anatomy and Physiology

The heart is a strong, muscular pump that circulates blood throughout the body. Each day, the heart beats approximately 100,000 times and pumps 2,000 gallons of blood. The heart consists of four chambers: the right atrium, which accepts deoxygenated blood from the body via the venous system; the right ventricle, which pumps that deoxygenated blood to the lungs via the pulmonary artery; the left atrium, which accepts newly oxygenated blood from the pulmonary veins; and the left ventricle, which pumps oxygenated blood to the rest of the body via the aorta. Four one-way, pressure-activated valves separate these four chambers. The tricuspid valve is a three-flap valve that separates the right atrium from the right ventricle. The pulmonary valve is a three-flap valve that separates the right ventricle from the pulmonary artery. The mitral valve is a double-leaflet valve that separates the left atrium from the left ventricle; it may also be called the bicuspid valve because of its construction. Finally, the aortic valve is a three-flap valve that separates the left ventricle from the aorta (see Figure 1; Hinkle & Cheever, 2018).

Figure 1

Anatomy of the Heart

(Blausen Medical Communications, Inc., 2013)

The contraction of the heart muscle is a highly coordinated and precisely timed series of events. During diastole, the atria fill from the venous system (i.e., the superior vena cava and left pulmonary veins), and passive filling of the ventricles occurs. The atria contract simultaneously, filling the ventricles with the remainder of the blood via the open mitral and tricuspid valves, also known as the atrioventricular or AV valves. During systole, both ventricles contract, closing the mitral and tricuspid valves (creating the S1 sound) and opening the aortic and pulmonary valves (or semilunar valves) to eject the blood into the pulmonary arteries and aorta. Once empty, decreased pressure inside the ventricles causes the semilunar valves to close again while the atria fill. This valve closure causes the second heart sound, or S2, which marks the start of diastole. Ventricular filling may be heard as S3, or if the ventricles are resistant and filling is slow, S4 (see Figure 2; Hinkle and Cheever, 2018).

Figure 2

Circulation of Blood Through the Heart

(Christinelmiller, 2020)

The respiratory system facilitates life-sustaining processes, including oxygen transport, respiration, ventilation, and gas exchange. Human cells rely on the oxidation of carbohydrates, fats, and proteins to produce energy. Without a continuous supply of oxygen, cells in the brain, heart, and other essential organs cannot survive. Oxygen is transported to, and carbon dioxide is removed from, the circulating blood through the thin walls of the capillaries. Oxygen diffuses through capillary walls to the interstitial fluid and eventually to the cells. Carbon dioxide diffuses in the opposite direction from the cells to the blood. After these tissue capillary exchanges, blood enters the systemic venous circulation and travels to the pulmonary circulation. The oxygen concentration in the alveoli is higher than the concentration in the blood; therefore, oxygen diffuses from the alveoli to the blood. Similarly, carbon dioxide has a higher concentration in the blood than in the alveoli, so it diffuses from the blood to the alveoli (see Figure 3; Hinkle & Cheever, 2018).

Figure 3

Human Gas Exchange

                                                                                                                                  (Medic Tests, 2021)

Extracorporeal Membrane Oxygenation (ECMO)

ECMO is a circuit that consists of a mechanical pump, a membrane oxygenator (i.e., membrane lung), and a heat exchanger. The circuit drains blood from the venous vascular system through a catheter, circulates in a pump outside the body, and is reinfused into the body through an arterial or secondary venous vascular access site. Gas exchange (i.e., oxygenation and decarboxylation) occur at the membrane lung, which consists of thin, semipermeable, hollow fiber tubes that mimic the role of alveoli within the lungs. Rewarming of the treated blood to body temperature also occurs at the site of the membranous lung. Preparing a patient for ECMO requires surgery, where cannulas (i.e., plastic tubes) are inserted into large arteries or veins in the neck, chest, or groin. Deoxygenated blood is extracted from the venous catheter and is pumped to the membranous lung, where gas exchange occurs. Air and oxygen flow through the hollow fibers in the membranous lung oxygenator. As the blood passes through the fibers, oxygen moves from the fibers to the red blood cells (RBCs). Carbon dioxide moves from the blood into the fibers and is removed with the exhaust gas. The oxygenated blood is then carried back to the patient through a different catheter (see Figure 4). There are two types of ECMO: venovenous (VV) and venoarterial (VA; Vyas & Bishop, 2022; Wrisinger & Thompson, 2022).

Figure 4

ECMO Schema

(Schaub, 2007)

Venovenous ECMO

VV ECMO provides only respiratory support and is used for patients with primary respiratory failure who are hemodynamically stable (i.e., preserved cardiac pump function) but are refractory to treatment, including MV. The primary goal of VV ECMO is to provide lung-protective ventilation, allowing time for lung rest and healing. There are two approaches to VV ECMO: single and double venous cannula. A single venous cannula involves the extraction of blood from the vena cava or the right atrium, circulated through the membranous lung, and returned to the right atrium. A Seldinger technique (i.e., a guide wire) is used to place the single cannula into the right internal jugular vein. The main benefit of a single cannula VV technique is that the patient has only one cannula in the neck and no cannula in the groin, allowing patients to get out of bed once they are extubated. The cannula is also flexible and kink resistant. The single-lumen approach is also beneficial for pediatric patients whose femoral veins may not be large enough to support the insertion of a cannula. The single cannula technique has some disadvantages, including being more sensitive to movements that can affect the cannula's flow. In addition, the single cannulas are often smaller Fr sizes, which can reduce the peak flow of the circuit, and placement must be completed under transesophageal guidance. Proper placement of a single cannula VV ECMO is critical because the displacement of the cannula can prevent newly oxygenated blood from being distributed throughout the body (Makdisi & Wang, 2015; Vyas & Bishop, 2022).

VV ECMO can also be performed using a double venous cannula. With this approach, a drainage (i.e., outflow) cannula is placed in the right internal jugular, and an infusion (i.e., inflow) cannula is placed in either the right or left femoral veins (see Figure 5). Most ECMO centers will use a femoral-right internal jugular (RIJ) approach, with the drainage cannula in the right internal jugular vein with the tip at the superior vena cava-right atrium (SVC-RA) junction and the infusion cannula (i.e., oxygenated blood) in the femoral vein with the tip inferior to the right atrium-inferior vena cava (RA-IVC) junction. This approach can decrease the risk of recirculation (i.e., when reinfused oxygenated blood is withdrawn through the drainage cannula without passing through systemic circulation). Recirculation is a phenomenon that only occurs with VV ECMO. A secondary dual cannulation approach is the femoral-femoral strategy, where the infusion and drainage cannulas are placed in the femoral veins. This approach does have a higher risk of recirculation. Dual cannula VV ECMO does have disadvantages, including increased risk of femoral site infection and limited mobility (Manaker, 2022; Rosario & Ambati, 2022; Vyas & Bishop, 2022; Wrisinger & Thompson, 2022).

Figure 5

Venovenous (VV) ECMO for Isolated Respiratory Failure

(Van Meurs et al., 2012)

Venoarterial ECMO

VA ECMO provides respiratory and mechanical circulatory support parallel to the native cardiac function. This type of ECMO is used for patients with cardiac or cardiopulmonary failure. The VA ECMO and VV ECMO circuits are similar, except the VA ECMO drainage cannula is placed into an artery to provide circulatory support to the patient. There are two approaches to VA ECMO cannulation, central and peripheral. Central cannulation occurs when the venous infusion cannula is placed in the right atrium and the discharge cannula in the ascending aorta. This approach is used for patients who had cardiac surgery and are failing to wean from CPB despite high dose inotropic or vasopressor support. These patients often had poor intraoperative myocardial protection, incomplete revascularization, or preexisting heart failure. Peripheral cannulation is used for patients with cardiogenic shock or cardiac arrest. This approach is performed by placing a venous infusion cannula in either a femoral or the right internal jugular vein and placing an arterial drainage cannula in the femoral artery or grafting it onto the right subclavian or axillary artery (Manaker, 2022; Rosario & Ambati, 2022; Vyas & Bishop, 2022; Wrisinger & Thompson, 2022).

Indications for ECMO

ECMO can provide cardiopulmonary life support for adults, children, and neonates who are acutely ill. Appropriate patient selection for VV and VA ECMO is essential to prevent adverse outcomes. Patients being considered for VV ECMO should be assessed to rule out irreversible disease processes (i.e., severe neurological injury, end-stage malignancy) that would contraindicate ECMO. The ELSO provides guidelines that describe the indications and the practice of ECMO for adults, children, and neonates. VV ECMO provides respiratory support for patients who do not respond to conventional medical therapy and MV or have acute, potentially reversible respiratory failure. VV ECMO's primary goals are to promote lung rest, facilitate earlier ventilation weaning and mobilization, and decrease the likelihood of multiorgan dysfunction and mortality (Makdisi & Wang, 2015; Tonna et al., 2021; Vyas & Bishop, 2022; Wrisinger & Thompson, 2022). Other indications for respiratory support include:

• ARDS secondary to viral or bacterial pneumonia
• COVID-19 severe respiratory failure
• pulmonary embolism (PE)
• aspiration (e.g., meconium)
• influenza
• pulmonary support in cases of airway obstruction, smoke inhalation, air leak syndrome, pulmonary contusion (barotrauma), drowning, hypercapnia, or hypoxic respiratory failure
• status asthmaticus
• bridge to lung transplant
• support for lung resections in unstable patients
• massive hemoptysis or pulmonary hemorrhage
• bronchopleural fistula
• congenital diaphragmatic hernia (Makdisi & Wang, 2015; Tonna et al., 2021; Vyas & Bishop, 2022; Wrisinger & Thompson, 2022)

The ELSO guidelines provide more specific recommendations for patients who should receive VV ECMO, including patients with ARDS and refractory hypoxemia (PaO₂/FiO₂ <80 mmHg) or severe hypercapnic respiratory failure (pH <7.25 with a PaCO₂ ≥ 60 mmHg). There is no absolute contraindication for starting ECMO except the anticipated nonrecovery without a plan for viable decannulation (Makdisi & Wang, 2015; Tonna et al., 2021). The ELSO guidelines recognize the following as relative contraindications for VV ECMO:

• older age (no established threshold; some sources recommend over 70)
• systemic bleeding
• irreversible or incapacitating central nervous system pathology
• MV for more than 7 days with a plateau pressure > 30 cm H₂O and FiO₂ >90%
• immunosuppression
• pulmonary hypertension (i.e., mean pulmonary artery pressure > 50 mmHg)
• contraindications to anticoagulation
• central nervous system hemorrhage (Makdisi & Wang, 2015; Tonna et al., 2021)

VA ECMO provides respiratory and mechanical circulatory support for patients with isolated cardiac or cardiopulmonary failure. Appropriate patient selection for VA ECMO is critical because mortality rates are 50% to 60%, and the 6-month survivorship is 30%. Similar to VV ECMO, patients considered for VA ECMO should be assessed to rule out irreversible disease processes. In addition, potential candidates should have an echocardiogram to characterize the cardiac pathology. Patients should be considered for VA ECMO when they have low cardiac output and hypotension (systolic blood pressure < 90 mmHg) despite inotropic and intra-aortic balloon pump support (Lorusso et al., 2021; Manaker, 2022; Wrisinger & Thompson, 2022). Indications for VA ECMO can include the following:

• cardiac arrest with ongoing CPR (i.e., witnessed arrest, recurrent ventricular fibrillation [VF], or intermittent return of spontaneous circulation [ROSC])
• acute, chronic heart failure
• acute heart failure secondary to myocarditis
• mediastinal mass
• refractory ventricular tachycardia
• massive PE
• refractory cardiogenic shock secondary to acute coronary syndrome, drug toxicity, cardiac trauma, anaphylaxis, and sepsis leading to cardiac depression
• postcardiotomy shock
• hypothermia
• periprocedural for high-risk cardiac interventions
• post heart transplantation
• bridge to long-term ventricular assist device (VAD) support or heart/lung transplantation (Lorusso et al., 2021; Manaker, 2022; Wrisinger & Thompson, 2022)

The ELSO also provides guidance on contraindications for VA ECMO. Ideally, VA ECMO should be initiated before multiorgan failure, and healthcare providers (HCPs) should consider the patient's age, comorbidities, and prognosis based on the underlying illness. Similar to VV ECMO, the only absolute contraindication to VA ECMO is a preexisting or underlying condition that is incompatible with recovery (e.g., severe neurological injury, end-stage malignancy, unwitnessed cardiac arrest, not a transplant or VAD candidate, unrepaired aortic dissection, severe aortic regurgitation, or a lethal chromosomal abnormality). Additional contraindications for VA ECMO include severe vascular disease with extensive aortic and peripheral vessel involvement, a severe immunologic disease with marked blood and coagulation disorders, and liver cirrhosis (Lorusso et al., 2021; Manaker, 2022; Wrisinger & Thompson, 2022).

Equipment and Personnel

The ECMO circuit consists of a pump, membrane lung (oxygenator and heat exchanger), and drainage and infusion cannula. There are two types of pumps used with ECMO: centrifugal and roller. Centrifugal pumps contain plastic cones that rotate at 3,000 revolutions per minute, generating up to 900 mmHg of pressure that propels the blood in the pump. The negative pressure of 400 to 500 mmHg helps prevent microemboli and cavitations. Blood flow in the pump is preload and afterload dependent. For patients with hypovolemia, the inlet pressure becomes more negative to maintain the speed of the pump. For VA EMCO, changes in circuit flow and speed of the pump are impacted by changes in systemic vascular resistance. The roller pump comprises a rotating arm with rollers compressing the tubing to propel the blood. In contrast to centrifugal pumps, roller pump speed and flow rate are decreased with hypovolemia. In addition, roller pumps are not controlled by afterload; therefore, systemic vascular resistance does not influence blood pumping. Roller pumps are safer, more reliable, and less expensive. However, microembolization shredding can occur due to high negative pressure (Vyas & Bishop, 2022).

As discussed above, the membrane lung comprises microporous polypropylene hollow fiber or non-microporous silicone rubber. Membrane oxygenators that allow less particulate and gas embolization than bubbles will have superior gas exchange. Polypropylene hollow fiber oxygenators are superior to silicone oxygenators due to their small priming volume, low resistance, and high gas transfer. A new generation oxygenator, made of polymethyl pentene, has shown improved gas exchange and reduced platelet and RBC transfusion. Polyvinyl tubing and polycarbonate connectors are used in the ECMO circuit. The benefits of polyvinyl tubing are its compatibility with blood, resistance to kinking, flexibility, smoothness, and transparency. The drainage cannula should be 23 Fr to 25 Fr, while the infusion cannula should be 17 Fr to 21 Fr. A 25 Fr multistage femoral venous catheter (i.e., numerous side holes that provide drainage) may be helpful for patients who require a flow of more than 6 L/min. Finally, all ECMO circuits have an oxygen supply (FiO₂) and sweep gas flowmeters. Sweep gas allows for low tidal volume ventilation and carbon dioxide removal (Vyas & Bishop, 2022; Wrisinger & Thompson, 2022).

Finally, the ECMO team usually consists of a cardiothoracic/vascular surgeon or interventional cardiologist who performs the cannulation. For VA ECMO, central access occurs through a sternotomy that a cardiothoracic surgeon performs. Peripheral access can be performed percutaneously in an ICU or cardiac catheterization lab. The team also includes a perfusionist, intensivist, respiratory therapist, ECMO specialist, and bedside nurse. The ECMO specialist is specialty trained to handle the ECMO circuit to meet the patient's clinical needs under the guidance of an ECMO-trained provider (Vyas & Bishop, 2022; Wrisinger & Thompson, 2022).

Preparation for ECMO

Before initiating VV or VA ECMO, the HCP should thoroughly evaluate the patient to determine whether the underlying disease process is reversible. Echocardiography should be performed to determine if there is a cardiac etiology and to ensure that there is near-normal cardiac function. For patients with respiratory failure, with no evidence of cardiac etiology and near-normal cardiac function, VV ECMO can be initiated. VA ECMO should be used for patients with cardiac etiology or compromised cardiac function. Approximately 10% of patients with respiratory failure will develop right ventricular (RV) dysfunction due to hypercarbia, acidosis, and hypoxemia with ARDS. Most patients with RV dysfunction can still be maintained on VV ECMO using inotropes, pulmonary vasodilators, diuretics, and optimizing their acid-base balance. These strategies will reduce RV afterload and promote gas exchange. VA ECMO may be needed for patients with refractory hypotension after VV ECMO cannulation. HCPs can use the respiratory ECMO survival prediction (RESP) score, developed by ELSO and The Department of Intensive Care at The Alfred Hospital in Melbourne, to assist in predicting survival with the initiation of VV ECMO. Since ECMO is an expensive, labor and resource-intensive intervention, this tool can help create risk/benefit benchmarks. However, it is recommended that ECMO initiation be based on clinical judgment and not solely on the predictor score, see Table 2 for the RESP criteria. Once the score is calculated, the HCP can plot the score on the estimated survival graph provided on the website. A score of 0 represents about 50% mortality, scores above 0 represent greater than 50% mortality, and scores below 0 represent lower than 50% mortality (Schmidt et al., 2014; Wrisinger & Thompson, 2022).

Table 2

Respiratory ECMO Survival Prediction (RESP) Score

RESP Criteria	Score
Age	18-49 (0) 50-59 (-2) > 60 (-3)
Immunocompromised status	No (0) Yes (-2)
Mechanically ventilated before ECMO	< 48 hours (+3) 48 hours - 7 days (+1) > 7 days (0)
Diagnosis	Asthma (+11) Bacterial pneumonia (+3) Trauma or burn (+3) Viral pneumonia (+3) Aspiration pneumonitis (+5) Other acute respiratory diagnoses (+1) Nonrespiratory or chronic respiratory diagnosis (0)
History of central nervous system (CNS) dysfunction	No (0) Yes (-7)
Neuromuscular blockage before ECMO	No (0) Yes (+1)
Acute-associated nonpulmonary infection	No (0) Yes (-3)
Nitric oxide before ECMO	No (0) Yes (-1)
Bicarbonate infusion before ECMO	No (0) Yes (-2)
Cardiac arrest before ECMO	No (0) Yes (-2)
PaCO2 > 75 mmHg	No (0) Yes (-1)
Peak inspiratory pressure > 42 cm H2O	No (0) Yes (-1)

(Schmidt et al., 2014; Wrisinger & Thompson, 2022)

HCPs must perform a similar evaluation before the initiation of VA ECMO. Similar to VV ECMO, HCPs should determine that there are no irreversible underlying disease processes. An echocardiogram should be done to ensure no greater than mild aortic insufficiency is present due to the risk of severe left ventricular (LV) distention. The ECMO team should place a large bore central venous access device and an arterial line before cannulation to allow for hemodynamic monitoring and fluid or blood product administration. The survival after venoarterial ECMO (SAVE) score may be used to predict survival in refractory cardiogenic shock requiring VA ECMO. See Table 3 for the SAVE criteria. Once the total score is calculated, the HCP can determine the risk class and survival percentage using the SAVE scoring, see Table 4 (Lorusso et al., 2021; Wrisinger & Thompson, 2022).

Table 3

The Survival After Venoarterial ECMO (SAVE) Score

SAVE Criteria	Score
Acute cardiogenic shock diagnosis group (select one or more)	Myocarditis (3) Refractory VT/VF (2) Congenital heart disease (-3) Post-heart or lung transplantation (3) Other diagnoses leading to cardiogenic shock (0)
Age	18-38 (7) 39-52 (4) 53-62 (3) ≥ 63 (0)
Weight (kg)	≤ 65 (1) 65-89 (2) ≥ 90 (0)
Acute pre-ECMO organ failures (select one or more) detailed criteria to define these conditions can be found on the website	Liver failure (-3) CNS dysfunction (-3) Renal failure (-3) Chronic renal failure (-6)
Duration of intubation before initiation of ECMO (hours)	≤ 10 (0) 11-29 (-2) ≥ 30 (-4)
Peak inspiratory pressure ≤ 20 cm H2O	(3)
Pre-ECMO cardiac arrest	(-2)
Diastolic blood pressure before ECMO ≥ 40 mm Hg	(3)
Pulse pressure before ECMO ≤ 20 mm Hg	(-2)
Bicarbonate before ECMO ≤ 15 mmol/L	(-3)
Constant value to add to all calculations of the SAVE score	(-6)
Total Score	-35 to 17

(Lorusso et al., 2021)

Table 4

SAVE Score, Risk Class, and Survival Percentage

Total Score	Risk Class	Survival Percentage
> 5	I	75
1 to 5	II	58
-4 to 0	III	42
-9 to -5	IV	30
≤ -10	V	18

(Lorusso et al., 2021)

Before initiating ECMO, the team must decide which type of ECMO is most appropriate based on the patient's needs and underlying etiology. The amount of oxygen the membrane lung provides is directly related to blood flow, with 3 to 6 L/min of blood flow required for VV ECMO to achieve acceptable arterial oxygenation. With VV ECMO, arterial oxygenation is also partially dependent on the cardiac output of the patient and the hemoglobin concentration and saturation. VA ECMO is a much better approach for improving systemic oxygenation because the oxygenated blood mixes with the arterial blood and directly perfuses the distal organs (Makdisi & Wang, 2015). Table 5 depicts the differences between VV and VA ECMO.

Table 5

Differences between VV and VA ECMO

VV ECMO	VA ECMO
Does not provide cardiac support to assist systemic circulation	Does provide cardiac support to assist systemic circulation
Requires only venous cannulation	Requires venous and arterial cannulation
Maintains pulmonary blood flow	Bypasses pulmonary circulation and decreases pulmonary artery pressures
Cannot be used with RV failure	Can be used with RV failure
Higher perfusion rates accepted	Lower perfusion rates accepted
Lower PaO2 achieved	Higher PaO2 achieved
ECMO circuit connected in series to the heart and lungs	ECMO circuit connected in parallel to the heart and lungs

(Makdisi & Wang, 2015)

Anticoagulation

Once it has been determined that ECMO will be initiated, the patient must be anticoagulated, usually with intravenous (IV) heparin. This is because the surfaces of the ECMO circuit elicit a systemic inflammatory response when blood is exposed to the circuit. The contact of the blood with the artificial surfaces causes the release of pro-inflammatory cytokines, leading to a hypercoagulable state. Unfractionated heparin (UFH) works by binding to antithrombin, which impairs thrombin, thus preventing thromboembolism formation. HCPs must monitor anticoagulation during ECMO to find a balance between reducing platelet and thrombin activation and providing sufficient clotting to prevent bleeding. Activated clotting time (ACT) is the most widely used test to monitor anticoagulation. However, the accuracy of this measurement can vary by sample size, temperature, age, hemodilution, antithrombin level, maturity of the coagulation system, platelet dysfunction, and ongoing synthesis of thrombin. The recommended ACT range for ECMO is 180 to 220 seconds (Szymanski, 2022; Vyas & Bishop, 2022).

Thromboelastography (TEG) is also frequently used to monitor the coagulation profile, including the strength and dissolution of clots. TEG is a whole blood clot test initially discovered in the late 1940s that examines whole blood clot strength over time. It has recently gained support for its successful use in cardiac surgery and liver transplantation. Other institutions may use activated partial thromboplastin time (APTT) for patients on heparin. In some studies, APTT was superior in monitoring anticoagulation because ACT could not delineate between low and moderate levels of anticoagulation. UFH is the first choice for anticoagulation in patients undergoing ECMO because it is inexpensive, has a rapid onset, is well tolerated by adults and children, and is easily reversible. The initial dosing for UFH is a 50 to 100 units/kg bolus, followed by 20 to 50 units/kg/hr titrated to achieve an ACT of 180 to 220 seconds (or based on the choice of anticoagulation monitoring used by the institution). Depending on thrombin generation and metabolic rates, the dosing may vary in adults and children (Szymanski, 2022; Vyas & Bishop, 2022).

Direct thrombin inhibitors (DTIs) are alternative anticoagulants for patients with heparin allergies or those who have a history of or developed heparin-induced thrombocytopenia (HIT) during ECMO. These medications bind directly to thrombin, and their effect is independent of antithrombin levels, eliciting a more predictable response. However, there are no reversal agents for DTIs if severe or life-threatening bleeding occurs. Argatroban (Acova) initial dosing ranges from 0.2 to 0.5 mcg/kg/min. Bivalirudin (Angiomax) initial doing is 0.025 to 0.05 mcg/kg/min (Szymanski, 2022; Vyas & Bishop, 2022).

Initiation, Maintenance, and Weaning of ECMO

Once it has been decided that ECMO is appropriate, the ECMO team should determine whether VV or VA will be needed. For patients receiving VV ECMO, the team must decide between the various cannula placement options, femoro-atrial, femoro-femoral, or dual lumen drainage and return cannula (single cannula). The advantages and disadvantages of these approaches are discussed above. For patients who need respiratory and cardiac support, VA ECMO is appropriate. ECMO cannulation is recommended within 10 to 20 minutes after failed resuscitation efforts for patients in cardiac arrest. Delayed ECMO initiation can increase the risk of a hypoxic brain injury or organ failure. The ECMO team will need to decide between peripheral and central VA ECMO. Peripheral VA ECMO with a Seldinger technique is not recommended for patients with peripheral vascular disease. If LV dysfunction or poor ventricular contractility leads to distention of the LV, switching to central VA ECMO is recommended (Manaker, 2022; Vyas & Bishop, 2022). The following steps can be followed to initiate ECMO (Vyas & Bishop, 2022):

• Insert the cannula. The largest cannulae that can be placed in the vessels are used. Cannulation placement is confirmed by echocardiography or fluoroscopy in VA ECMO.
• Connect the ECMO circuit and remove all air from the circuit.
• Check for gases.
• Check the circuit, oxygenation membrane, and connections for air bubbles.
• Connect the sweep gas flow to the oxygenator. The initial flow should be 3 to 4 L/min.
• Increase revolutions per minute (RPM) until adequate positive pressure is present in the return limb of the circuit.
• Remove clamps on the circuit and ensure antegrade blood flow of ECMO.
• Increase RPM to achieve 3 to 4 L/min of blood flow.
• Discontinue mechanical compressions if in cardiac arrest.

Once the patient is connected to the ECMO circuit, blood flow is increased until respiratory and hemodynamic parameters are within desired ranges. The target range or arterial oxyhemoglobin saturation is above 90% for VA ECMO and above 70% for VV ECMO. The target range for venous oxyhemoglobin saturation is 20% to 25% lower than arterial saturation. Arterial blood pressure, venous oxygen saturation, and blood lactate level can be used to determine adequate tissue perfusion. Vasopressors are used to ensure an adequate mean arterial pressure (MAP). Titration should occur to ensure that MAP is greater than 60 mm Hg for adequate organ perfusion and less than 80 mm Hg to prevent LV distention and dysfunction (Manaker, 2022; Vyas & Bishop, 2022).

Maintenance

Once ECMO has been initiated, the HCP will need to monitor sedation and analgesia to ensure that the patient is comfortable. The blood flow rate of ECMO is maintained once respiratory and hemodynamic target goals are achieved. The HCP may need to make frequent adjustments based on the continuous venous oximetry values in the venous limb of the circuit. If venous oxyhemoglobin saturation is below the target goal, possible interventions can include increasing the blood flow, hemoglobin concentration, or intravascular volume. Reducing body temperature may also help by decreasing systemic oxygen uptake. The ideal targeted temperature is 33 to 36 degrees Celsius for the first 24 hours, followed by gradual rewarming to 37 degrees Celsius. Platelet counts should be frequently monitored because platelets are continuously consumed during ECMO. HCPs should ensure that platelet levels are maintained above 150,000/microliter; platelet infusions are required if the level drops below this target (Manaker, 2022; Vyas & Bishop, 2022).

Oxygen delivery depends on the amount of hemoglobin and blood flow for patients on ECMO. Given the risks associated with high blood flow in ECMO, blood transfusion is recommended to increase oxygen levels when necessary. Hemoglobin levels for patients on ECMO are maintained at over 12 g/dL. Ventilator settings are reduced during ECMO to avoid oxygen toxicity and other complications such as barotrauma or a ventilator-induced lung injury. The target plateau pressure should be maintained at less than 20 cm H₂O and FiO₂ less than 0.5. Other recommended ventilator settings include positive end-expiratory pressure (PEEP) of greater than 10 cm H2O, respiratory rate of 4 to 8 breaths/minute, and tidal volume (TV) of less than 100 mL. If patients are fluid overloaded after ECMO initiation, aggressive diuresis is needed once the patient is stable. For patients receiving VA ECMO, LV monitoring is critical. LV output can be closely monitored by identifying pulsatility in the arterial line waveform and routine echocardiography. Inotropes (i.e., dobutamine [Dobutex], milrinone [Primacor]) and an intra-aortic balloon pump can improve LV output. If LV ejection cannot be improved with these measures, an immediate LV decompression is critical to avoid pulmonary hemorrhage (Manaker, 2022; Vyas & Bishop, 2022). Additional management strategies for patients on ECMO include the following (Manaker, 2022; Vyas & Bishop, 2022):

• Pulmonary management includes daily chest radiographs, frequent posture changes, endotracheal suctioning every 4 to 6 hours, and flexible bronchoscopy when needed.
• Renal system management: During the first 20 to 48 hours of ECMO, acute inflammation leads to capillary leak and intravascular volume depletion, resulting in oliguria (oliguric phase). After 48 hours, the diuretic phase begins. Diuretics are required if the oliguric phase persists for more than 48 to 72 hours. Continuous renal replacement therapy (CRRT) is not recommended in an acute kidney injury on ECMO due to the increased mortality risk.
• CNS management includes regular neurological examinations and sedation vacations. Aggressive management is recommended for seizures.
• Strict monitoring for infection and sepsis is recommended. Weekly pan cultures and more frequently as needed for suspicion of infection are recommended.
• Close monitoring of nutrition, fluid, and electrolytes is required. Total parenteral nutrition (TPN) can deliver fluids, electrolytes, glucose, vitamins, minerals, lipids, and proteins through venous infusion.

Weaning

ECMO should be discontinued as soon as it is safe to do so. However, determining when to wean is not well-established and is often provider or institutional-dependent. Generally, pulmonary function recovery takes 1 to 3 weeks. For patients with respiratory failure on VV ECMO, improvements in arterial oxyhemoglobin saturation, pulmonary compliance, and radiographic appearance may indicate that patients are ready to wean. However, one or more trials are recommended before permanently discontinuing ECMO. VV ECMO weaning trials are performed by eliminating all countercurrent sweep gas through the oxygenator while blood flow remains constant. HCPs should observe the patient for several hours and adjust the ventilator settings to maintain adequate oxygenation and ventilation (Manaker, 2022; Vyas & Bishop, 2022; Wrisinger & Thompson, 2022).

For patients on VA ECMO, enhanced aortic pulsatility is associated with improved LV output, which indicates that the patient may be ready to wean. Other indications that native cardiac function is restored include decreasing central venous and/or pulmonary pressures or increasing blood pressure. Before attempting a VA ECMO weaning attempt, inotropic and vasopressor medication should be titrated to low doses. The arterial line should remain in place for hemodynamic monitoring during the weaning trial. Although there is no standardized approach to weaning, most organizations use a 3-step approach. This approach involves daily weaning studies with bedside assessment for decannulation, followed by a formal turndown study under transesophageal (TEE) guidance for decannulation in the operating room. Daily weaning attempts should have incremental decreases in flow by 0.5 liters L/min to a minimum of 2 L/min. If the MAP does not fall more than 10 to 15 mm Hg and filling pressures are not significantly increased, then hemodynamics are trended for 8 hours. Once the weaning trial is tolerated, a bedside assessment for decannulation is performed by decreasing the flow to 1 L/min and monitoring hemodynamics. If the bedside assessment is successful, the patient is scheduled for a formal turndown in the operating room, where ECMO flow is decreased, and the cannulae are clamped for 30 minutes to 4 hours. If this turndown is successful, the patient can be decannulated by surgically repairing the arteriotomy site (Manaker, 2022; Vyas & Bishop, 2022; Wrisinger & Thompson, 2022).

Complications

Patients requiring VV or VA ECMO are critically ill due to respiratory or cardiopulmonary failure. ECMO can be a life-saving intervention for some patients, but it is not without the risk of complications. Bleeding is the most common and life-threatening complication related to ECMO. Other complications include gas embolism, thromboembolism, intracardiac thrombosis, mechanical complications, HIT, renal failure, sepsis, hypoxia, hypotension, mental health issues, cannula-related complications, and neurological, gastrointestinal, and metabolic complications.

Bleeding is the most common complication of ECMO, occurring in 30% to 50% of patients due to anticoagulation, fibrinolysis, platelet dysfunction, uremia, and hepatic dysfunction. Anticoagulation monitoring is critical to preventing serious bleeding, including intracranial hemorrhage or bleeding in the gastrointestinal (GI) tract or lungs. Intracranial hemorrhage occurs in 10% to 15% of patients with ARDS on ECMO, resulting in 43% of deaths. Therefore, it is recommended to avoid invasive or surgical procedures for patients on ECMO. In addition, it is recommended to keep the platelet count above 150,000, fibrinogen greater than 200 mg/L, prothrombin ratio less than 1.5, and lower ACT. If bleeding occurs, the temporary cessation of the heparin infusion can be considered. It is estimated that 17% of VV ECMO and 34% of VA ECMO patients require surgery for bleeding. Pulmonary hemorrhage can be controlled using steroids or bronchoscopy (Manaker, 2022; Vyas & Bishop, 2022). Other complications include (Manaker, 2022; Vyas & Bishop, 2022):

• Gas embolism can occur because the centrifugal pump creates a negative pressure of up to 100 mmHg between the drainage cannula and pump, leading to air entry from this part of the ECMO circuit.
• Intracardiac thrombosis can occur due to peripheral cannulation in VA ECMO through the femoral vein and artery, leading to retrograde blood flow to ascending aorta.
• Systemic thromboembolism occurs infrequently, but there is a higher risk with VA ECMO versus VV ECMO. Therefore, HCPs should monitor the ECMO circuit for clot formation and maintain ACT with the heparin infusion.
• Mechanical complications, including clot formation on the ECMO circuit, occur frequently. Heparin-coated circuits can help decrease clot formation.
• HIT infrequently occurs, seen mainly with patients on long-term ECMO. If HIT occurs, heparin should be stopped, and a DTI should be initiated.
• Sepsis can occur because ECMO is a foreign body that increases the risk for infection. Patients with postcardiotomy cardiogenic shock are more likely to develop an infection.
• Neurological complications can include seizures, infarctions, or intracranial hemorrhages.
• Renal failure and oliguria can occur during the initial phase of ECMO and may require hemofiltration or dialysis.
• GI tract complications can include hemorrhage, hyperbilirubinemia, and biliary calculi (from prolonged fasting, TPN, and diuretics).
• Metabolic complications can include electrolyte disturbances, hypoglycemia, hyperglycemia, and decreased kidney and liver function.
• Cannula-related complications can include cannula malposition, hemorrhage, incorrect location, pseudoaneurysm, vessel perforation, and limb ischemia.
• Hypoxia can occur due to inadequate circuit flow in VV ECMO. With VA ECMO, hypoxia can occur if the infusion catheter perfuses the lower extremities more than the upper extremities, brain, and heart. Other causes can include recirculation, sepsis, seizures, or inadequate sedation.

Post-Intensive-Care Syndrome (PICS)

Studies have found that ECMO survivors experience a phenomenon associated with long-term cognitive, mental, and physical impairments termed post-intensive-care syndrome (PICS). PICS refers to a group of problems patients can experience after surviving critical illnesses and MV (American Thoracic Society, 2020). PICS is characterized by prolonged impairment in cognition, mental health, and physical functioning that can persist for years following ICU admission (Lacomis, 2021). As many as 50% of patients who survive critical illness experience at least one PICS-associated complication, negatively impacting 5-year morbidity and mortality (American Thoracic Society, 2020). The physical impairments of PICS arise from patients who experienced ICU-acquired weakness (ICUAW, i.e., neuromuscular weakness secondary to critical illness, prolonged bed rest, and immobility), with long-term sequelae that can include persistent generalized weakness, poor mobility, falls, joint contractures, and an inability to perform ADLs. PICS can affect anyone who survives critical illness, even those who were healthy before their illness. People with existing chronic medical conditions such as lung disease or muscle disorders are at higher risk of developing PICS. In addition, people with psychiatric illness or cognitive impairment (e.g., dementia) are more likely to experience more severe symptoms after discharge. Patients receiving MV are at higher risk for developing PICS related to muscle weakness and the likelihood of having severe infections, acute respiratory distress syndrome (ARDS), hypoxia, ICU delirium, and hypotension (American Thoracic Society, 2020; Lacomis, 2021).

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